Liver cancer is known as one of the most fatal cancers in the world. In particular, it is reported that at least about five hundred thousand people die of liver cancer every year in Asia and in Sub-Saharan Africa. Liver cancer can be largely classified into hepatocellular carcinoma which arises from the liver cell itself, and metastatic liver cancer which is cancer from other tissues spread to the liver. About 90% of liver cancer is hepatocellular carcinoma, and the term liver cancer is generally understood to refer to hepatocellular carcinoma.
Prognosis of liver cancer refers to anticipating various conditions of the patient suffering from liver cancer such as possibility of full recovery from liver cancer, possibility of recurrence after treatment, possibility of survival of patient after being diagnosed of liver cancer, etc. This may vary depending on various conditions such as severity of the disease, diagnosis point, treatment progress, etc. Liver cancer can be treated efficiently only when various treatment methods are properly applied according to its prognosis. For example, with regard to patients who are estimated to have good prognosis, it would be necessary to avoid dangerous treatment methods which have a possibility to cause severe side effects to the patients such as aggressive chemical treatment or operations, radiation treatment, and select treatment methods which are relatively moderate, conservative and safe. On the other hand, with regard to patients who are estimated to have bad prognosis, chemical treatment or operations, treatment methods such as radiation treatment should be actively conducted in an attempt to increase the survival period or rate.
According to researchers conducted until now, the prognosis of liver cancer that has already progressed is extremely bad, and shows a high fatal rate of dying within 6 months from diagnosis, which leaves an average duration of life of only 4 months. However, liver cancer having a size of less than 3 cm has good prognosis, and is known to have a survival rate of 90% for a year without any particular treatment and after surgery, the survival rate of five years is about 40˜50%. However, it is very difficult to estimate the prognosis of liver cancer patients precisely with prior art technology. In order to estimate prognosis accurately, an analysis method which classifies patients into each risk group is required. However, until now, prognosis has been determined depending only on the clinical pathological liver cancer stage at the time of diagnosis and primary surgical treatment without a means for accurately estimating prognosis of liver cancer.
The conventional analysis methods include the BCLC (Barcelona-Clinic Liver Cancer) staging system. Said system is a system for classifying liver cancer patients to determine a treatment method (liver resection, liver transplantation or radiofrequency ablation, etc. according to the stage of the disease) by determining the stage of a patient's liver cancer before conducting surgery on the patient (Llovert J M, Bru C, Bruix J. Prognosis of hepatocellular carcinoma: the BCLC staging classification. Semin Liver Dis. 1999; 19(3):329-338).
However, unfortunately, the prognosis of each liver cancer patient cannot be precisely determined by the liver cancer stage alone. Thus, it is necessary to develop a technology using gene markers to predict prognosis of liver cancer patients accurately. That is, by selecting patients expected to respond well to a specific treatment method (for example, liver resection) based on the stage and the prognosis result of each individual patient and providing the treatment to the patients, the overall treatment outcomes of liver cancer patients can be improved, and socioeconomic effects such as saving medical cost can be expected.
Meanwhile, with regard to UVRAG, NAMPT, STAT3, CIAP2, BHLHE41, MMP2, SESN2, HMGB1, SIRT1, RPS19BP1, LAMP2, AGER, SESN3, ID2, TCF3, HMGB2, TP63, RAGE, KIAA1967, SATB1, RAPTOR, SESN1, CCNG2, CDH1, FASLG, CASP3, BECN1, CDH2, TWIST1, MMP9, VEGF, ATG12, DIABLO, E2F1, LAMP1, LC3, ATG7, TKT, AIFM1, BNIP3, ATG3, DRAM, ATG5, NNMT, PRKAA1, CASP8, ULK1, BCL2L1, FAS, CSE1L, FRAP1, AKT1, BAX, BCL2, PTEN, CBS, XIAP proteins, it is not known how their expression level or expression pattern in liver cancer tissues changes according to the stage of liver cancer and how they can be used for predicting prognosis of liver cancer according to stage. Although there have been cases using the above proteins or some of the genes encoding the above proteins as a marker for prognosis of liver cancer, there has not been a case using them as a marker for prognosis of liver cancer according to stage.
As a result of conducting a research on predicting prognosis of liver cancer, the present inventors found genes whose expression level and expression pattern vary significantly (according to the stage of liver cancer), and completed the present disclosure.